Targeted Therapies Drive Declining Multiple Myeloma Mortality in the United States

By: Wendy LaGrego
Posted: Friday, May 15, 2026

A new population-based analysis published in Oncotarget found that advances in targeted therapeutics have coincided with substantial declines in U.S. multiple myeloma (MM)–specific mortality over the past 5 decades. Led by Navkirat Kahlon, MD, of the Mass General Cancer Center at Wentworth-Douglass Hospital, Dover, New Hampshire, and colleagues, the study evaluated national mortality trends from 1975 to 2023 using Surveillance, Epidemiology, and End Results (SEER) data to better understand how evolving therapies have influenced real-world outcomes.  

Study Details 

The researchers conducted a retrospective, cross-sectional analysis using age-adjusted U.S. mortality data from SEER*Explorer. Adults aged 18 years or older who died from MM between January 1, 1975, and December 31, 2023, were included. Mortality trends were analyzed with Joinpoint regression modeling, which estimated annual percent change (APC) values and identified statistically significant shifts over time. To contextualize treatment evolution, the study period was divided into six intervals (1975–1994, 1994–2002, 2002–2009, 2009–2014, 2014–2021, and 2021–2023), reflecting broad therapeutic eras. 

Key Takeaways  

The analysis revealed that MM mortality steadily increased from 1975 to 1994, with an APC of +1.43% (P < .01), during a time when treatment options were largely limited to melphalan and corticosteroids. Mortality then began to decline modestly between 1994 and 2002 (APC = –0.70%; P = .02), coinciding with the adoption of autologous stem cell transplantation. A steeper decline occurred from 2002 to 2009 (APC = –1.85%; P < .01), aligning with the emergence of immunomodulatory drugs and proteasome inhibitors, including thalidomide and bortezomib.  

Mortality trends plateaued from 2009 to 2014, a period characterized by refinements within existing therapeutic classes rather than entirely new treatment approaches. However, from 2014 to 2021, mortality resumed declining (APC = –1.73%; P < .01), coinciding with the approval and broader use of monoclonal antibodies such as daratumumab and elotuzumab, maintenance therapy strategies, and triplet combinations.  

The most dramatic reduction in MM mortality occurred between 2021 and 2023, when the APC dropped by –5.64% (P < .01). Investigators noted that this period aligned with the clinical integration of CAR T-cell therapies and bispecific antibodies, including idecabtagene vicleucel, ciltacabtagene autoleucel, and teclistamab. According to the authors, “These approvals reflect a new phase in MM management, defined by immune-based precision therapies capable of inducing deep and durable responses in heavily pretreated patients.”  

The study also highlighted the broader implications of prolonged survival in MM. Although targeted therapies have transformed MM into a more manageable chronic disease, the authors emphasized that long-term treatment toxicities, health-care disparities, and escalating financial burdens remain significant concerns among this patient population. Geographic and socioeconomic barriers may limit access to newer therapies, particularly high-cost immunotherapies such as CAR T-cell products and bispecific antibodies.  

The investigators concluded that therapeutic innovation has fundamentally reshaped MM outcomes in the United States. “The declining MM-specific mortality rates over the past five 5 decades underscore the transformative impact of therapeutic innovation on patient survival,” the authors wrote, adding that emerging immunotherapies may drive even greater reductions in mortality as these agents move earlier in treatment algorithms and become incorporated into combination regimens. 

DISCLOSURE: For full disclosures of the study authors, visit oncotarget.com. 

Oncotarget

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